Regulation of Stearoyl Coenzyme A Desaturase 1 Gene Promoter in Bovine Mammary Cells

Martino, Orsola di; Troiano, Annaelena; Addi, Laura; Guarino, Andrea Maria; Calabrò, Serena; Tudisco, Raffaella; Murru, Nicoletta; Cutrignelli, Monica Isabella; Infascelli, F.; Calabrò, Viola

doi:10.1080/10495398.2015.1022182

Cited by 7 publications

(7 citation statements)

References 37 publications

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“…Overexpressing the SREBP1a factor validated the well-known crucial role of this factor for stimulation of SCD1 expression [ 30 ]. The results obtained with vectors expressing the factor series NFY-A, -B, -C are also in line with the respective literature in that we observed in the HepG2 model for liver cells a significant stimulation (cf [ 24 ]) and slight repression in the MAC-T model for MEC, similar as recently reported using the human breast cancer line MCF7 [ 59 ]. The pivotal role of the NFY factor family for the basal and nutritional regulated activity of the SCD1 promoter has recently been underscored in goat MEC model cells [ 60 ].…”

Section: Discussionsupporting

confidence: 92%

Stearoyl-CoA desaturase 1 expression is downregulated in liver and udder during E. coli mastitis through enhanced expression of repressive C/EBP factors and reduced expression of the inducer SREBP1A

Shen

Seyfert

2016

BMC Molecular Biol

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BackgroundStearoyl-CoA desaturase 1 (SCD1) desaturates long chain fatty acids and is therefore a key enzyme in fat catabolism. Its synthesis is downregulated in liver during illnesses caused by high levels of circulating lipopolysaccharide (LPS). SCD1 expression is known to be stimulated under adipogenic conditions through a variety of transcription factors, notably SREBP1 and C/EBPα and −β. However, mechanisms downregulating SCD1 expression during illness related reprograming of the metabolism were unknown. Escherichia coli elicited mastitis is an example of such a condition and was found to downregulates milk and milk fat synthesis. This is in part mediated through epigenetic mechanisms. We analyzed here mechanism controlling SCD1 expression in livers and udders from cows suffering from experimentally induced E. coli mastitis.ResultsWe validated with RT-qPCR that SCD1 expression was reduced in these organs of the experimental cows. They also featured decreased levels of mRNAs encoding SREBP1a but increased levels for C/EBP α and −β. Chromatin accessibility PCR (CHART) revealed that downregulation of SCD1 expression in liver was not caused by tighter chromatin compaction of the SCD1 promoter. Reporter gene analyses showed in liver (HepG2) and mammary epithelial (MAC-T) model cells that overexpression of SREBP1a expectedly activated the promoter, while unexpectedly C/EBPα and −β strongly quenched the promoter activity. Abrogation of two from among of the three C/EBP DNA-binding motifs of the promoter revealed that C/EBPα acts in cis but C/EBPβ in trans. Overexpressing truncated C/EBPα or −β factors lacking their repressive domains confirmed in both model cells the direct action of C/EBPα, but not of C/EBPβ on the promoter.ConclusionsWe found no evidence that epigenetic mechanism remodeling the chromatin compaction of the SCD1 promoter would contribute to downregulate SCD1 expression during infection. Instead, our data show for the first time that C/EBP factors may repress SCD1 expression in liver and udder rather than stimulating as it was previously shown in adipocytes. This cell type specific dual and opposite function of C/EBP factors for regulating SCD1 expression was previously unknown. Infection related activation of their expression combined with downregulated expression of SREBP1a explains reduced SCD1 expression in liver and udder during acute mastitis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12867-016-0069-5) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 92%

Stearoyl-CoA desaturase 1 expression is downregulated in liver and udder during E. coli mastitis through enhanced expression of repressive C/EBP factors and reduced expression of the inducer SREBP1A

Shen

Seyfert

2016

BMC Molecular Biol

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“…They up‐regulate expression of the target genes by binding to their own response element on the promoter of target genes (Karagianni and Talianidis, ; Kick et al, ). Research showed that sterol response element (SRE) sites are present in promoters of many genes related to fatty acid metabolism such as FASN, acetyl‐CoA carboxylase a ( ACACA ), SCD1 and acyl‐CoA synthase short‐chain family member 2 ( ACSS2 ) (di Martino et al, ). LXR can upregulate SREBF1 expression by binding to SRE and LXR response element sites on the SREBF‐1c promoter in ruminants (Xu et al, ).…”

Section: Discussionmentioning

confidence: 99%

MiR‐145 Regulates Lipogenesis in Goat Mammary Cells Via Targeting INSIG1 and Epigenetic Regulation of Lipid‐Related Genes

Wang

Shi

Luo

et al. 2016

Journal Cellular Physiology

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MicroRNAs (miRNAs) are noncoding RNA molecules that regulate gene expression at the post-transcriptional level to cause translational repression or degradation of targets. The profiles of miRNAs across stages of lactation in small ruminant species such as dairy goats is unknown. A small RNA library was constructed using tissue samples from mammary gland of Saanen dairy goats harvested at mid-lactation followed by sequencing via Solexa technology. A total of 796 conserved miRNAs, 263 new miRNAs, and 821 pre-miRNAs were uncovered. After comparative analyses of our sequence data with published mammary gland transcriptome data across different stages of lactation, a total of 37 miRNAs (including miR-145) had significant differences in expression over the lactation cycle. Further studies revealed that miR-145 regulates metabolism of fatty acids in goat mammary gland epithelial cells (GMEC). Compared with nonlactating mammary tissue, lactating mammary gland had a marked increase in expression of miR-145. Overexpression of miR-145 increased transcription of genes associated with milk fat synthesis resulting in greater fat droplet formation, triacylglycerol accumulation, and proportion of unsaturated fatty acids. In contrast, silencing of miR-145 impaired fatty acid synthesis. Inhibition of miR-145 increased methylation levels of fatty acid synthase (FASN), stearoyl-CoA desaturase 1 (SCD1), peroxisome proliferator-activated receptor gamma (PPARG), and sterol regulatory element binding transcription factor 1 (SREBF1). Luciferase reporter assays confirmed that insulin induced gene 1 (INSIG1) is a direct target of miR-145. These findings underscore the need for further studies to evaluate the potential for targeting miR-145 for improving beneficial milk components in ruminant milk. J. Cell. Physiol. 232: 1030-1040, 2017. © 2016 Wiley Periodicals, Inc.

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“…Accordingly, SCD and FASN have been found to be potential candidate genes influencing fatty acid composition in beef cattle. In dairy cattle, the high expression of SCD1 in the mammary gland is relevant for the fatty acid composition of milk and dairy products [35]. Interestingly, down regulation of SCD was found to have a positive correlation with serum glucose level in feed deprived ewes.…”

Section: Discussionmentioning

confidence: 96%

Gene expression pattern of acetyl-coA carboxylase alpha, fatty acid synthase, and stearoyl-CoA desaturase in pregnant Barki sheep under complete feed deprivation

2019

Mansoura Veterinary Medical Journal

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To assess the mRNA level of acetyl CoA carboxylase alpha (ACACA), fatty acid synthase (FASN), and stearoyl-CoA desaturase (SCD) by means of real-time PCR in Barki sheep subjected to complete feed deprivation. Design: Controlled study. Animals: Seven healthy pregnant ewes. Procedures: Ewes were subjected to complete feed deprivation with ad libitum water for five consecutive days. Venous blood samples were collected from each ewe before (zero time) and on the fifth day post-deprivation of feed for measurement of the mRNA level of ACACA, FASN, and SCD and assessment of serum metabolic profile parameters. Results: On the fifth day post-fasting, the gene expression pattern of ACACA, FASN, SCD genes showed a significant (p < 0.05) down regulation in comparison with pre-deprivation of feed. There was a significant (p < 0.05) increase in the serum level of non-esterified fatty acids (NEFA), beta-hydroxyl buteric acid (BHBA), and triglycerides in pregnant ewes in the fifth day post-fasting in comparison with predeprivation of feed. On the other hand, there was a significant (p < 0.05) decrease in the level of glucose, cholesterol, and insulin in pregnant ewes in the fifth day post-fasting compared with pre-deprivation of feed. On histopathology, liver showed marked heptic steatosis in midzonal and periportal area, with formation of small fatty cysts in liver lobule. There was a positive correlation between leptin and insulin (r = 0.996; p < 0.01), BHB and leptin (r = 0.951; p < 0.05) and glucose and SCD (r = 1.0, p < 0.01). However, there was a negative correlation between FASN and NEFA (r = -0.991; p < 0.05), FASN and leptin (r = -0.683; p < 0.05) and FASN and cholesterol (r = -0.82; p < 0.05). Conclusion and clinical relevance:Pregnant Barki ewes can clinically tolerate complete feed deprivation for five days, with down regulation of ACACA, FASN, SCD genes and presence of marked metabolic changes. Therefore, metabolic monitoring is warranted to predict the early changes associated with feed deprivation under different stressful conditions.

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Regulation of Stearoyl Coenzyme A Desaturase 1 Gene Promoter in Bovine Mammary Cells

Cited by 7 publications

References 37 publications

Stearoyl-CoA desaturase 1 expression is downregulated in liver and udder during E. coli mastitis through enhanced expression of repressive C/EBP factors and reduced expression of the inducer SREBP1A

Stearoyl-CoA desaturase 1 expression is downregulated in liver and udder during E. coli mastitis through enhanced expression of repressive C/EBP factors and reduced expression of the inducer SREBP1A

MiR‐145 Regulates Lipogenesis in Goat Mammary Cells Via Targeting INSIG1 and Epigenetic Regulation of Lipid‐Related Genes

Gene expression pattern of acetyl-coA carboxylase alpha, fatty acid synthase, and stearoyl-CoA desaturase in pregnant Barki sheep under complete feed deprivation

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